Neurodegenerative diseases or nerve injury can result in the loss of spinal motoneurons. However, remaining motoneurons after such insults show a variety of morphological and functional changes. As a consequence of both the loss of some motoneurons and the secondary changes in other, remaining motoneurons, functional restoration is poor, and the time course of recovery is protracted at best. The development of animal models, for example involving direct spinal cord damage or peripheral nerve injury, have begun to yield clues to both the mechanisms involved in motoneuron pathology and potential therapeutic approaches. Our work will concentrate on motoneuron dendrites, which are essential for the reception and integration of information. Dendrites in motoneurons atrophy after nerve injury or the death of neighboring motoneurons, and preventing that atrophy, or improving its recovery, in motoneurons that survive the initial insult will have a major impact on the restoration of spinal function. We have begun to develop two models in the adult rat spinal cord, utilizing induced motoneuron death or peripheral nerve cuts that will allow us to examine potential ways of preventing, or accelerating recovery from, dendritic atrophy in remaining motoneurons. In our first model, we found that the death of neighboring motoneurons causes the dendritic arbor of the remaining motoneurons to atrophy, but that manipulation of steroid hormones, specifically testosterone, can prevent or reverse that atrophy. Using morphological methods, we will determine if there is a dose/effect relationship for testosterone and dendritic protection, and if so, establish the minimum amount of testosterone required. We will also test the degree of functional recovery produced by these manipulations using electrophysiological methods. Using morphological methods, we will determine if there are critical temporal limits to the therapeutic window for protection from dendritic atrophy, and whether androgen prevents or accelerates recovery from dendritic atrophy. In our second model, we found an interactive effect of testosterone with brain-derived neurotrophic factor (BDNF) in preventing dendritic atrophy after cutting peripheral motor nerves. We will test whether the expression of BDNF in muscle or motoneurons, or its receptors, could be regulated by androgens, utilizing in situ hybridization and immunohistochemical techniques Together, results from studies using these two models will be informative about the therapeutic role for steroid hormones in treating spinal cord disease or nerve injury.